FOXA3_HUMAN
ID FOXA3_HUMAN Reviewed; 350 AA.
AC P55318; A9LYI5; Q53F16; Q9UMW9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Hepatocyte nuclear factor 3-gamma;
DE Short=HNF-3-gamma;
DE Short=HNF-3G;
DE AltName: Full=Fork head-related protein FKH H3;
DE AltName: Full=Forkhead box protein A3;
DE AltName: Full=Transcription factor 3G;
DE Short=TCF-3G;
GN Name=FOXA3; Synonyms=HNF3G, TCF3G;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=8499623;
RA Hromas R., Moore J., Johnston T., Socha C., Klemsz M.;
RT "Drosophila forkhead homologues are expressed in a lineage-restricted
RT manner in human hematopoietic cells.";
RL Blood 81:2854-2859(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10899756; DOI=10.1159/000022943;
RA Navas M.A., Vaisse C., Boger S., Heimesaat M., Kollee L.A., Stoffel M.;
RT "The human HNF-3 genes: cloning, partial sequence and mutation screening in
RT patients with impaired glucose homeostasis.";
RL Hum. Hered. 50:370-381(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Gastric mucosa;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROMOTER BINDING.
RX PubMed=9369482; DOI=10.1021/bi9703249;
RA Lin B., Morris D.W., Chou J.Y.;
RT "The role of HNF1alpha, HNF3gamma, and cyclic AMP in glucose-6-phosphatase
RT gene activation.";
RL Biochemistry 36:14096-14106(1997).
RN [9]
RP FUNCTION.
RX PubMed=12695546; DOI=10.1124/mol.63.5.1180;
RA Rodriguez-Antona C., Bort R., Jover R., Tindberg N., Ingelman-Sundberg M.,
RA Gomez-Lechon M.J., Castell J.V.;
RT "Transcriptional regulation of human CYP3A4 basal expression by CCAAT
RT enhancer-binding protein alpha and hepatocyte nuclear factor-3 gamma.";
RL Mol. Pharmacol. 63:1180-1189(2003).
RN [10]
RP INTERACTION WITH FOXA2.
RX PubMed=19919681; DOI=10.1186/gb-2009-10-11-r129;
RA Motallebipour M., Ameur A., Reddy Bysani M.S., Patra K., Wallerman O.,
RA Mangion J., Barker M.A., McKernan K.J., Komorowski J., Wadelius C.;
RT "Differential binding and co-binding pattern of FOXA1 and FOXA3 and their
RT relation to H3K4me3 in HepG2 cells revealed by ChIP-seq.";
RL Genome Biol. 10:R129.0-R129.0(2009).
RN [11]
RP PROMOTER-BINDING, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=19706729; DOI=10.1124/mol.109.055699;
RA Riffel A.K., Schuenemann E., Vyhlidal C.A.;
RT "Regulation of the CYP3A4 and CYP3A7 promoters by members of the nuclear
RT factor I transcription factor family.";
RL Mol. Pharmacol. 76:1104-1114(2009).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 115-215 IN COMPLEX WITH DNA.
RX PubMed=8332212; DOI=10.1038/364412a0;
RA Clark K.L., Halay E.D., Lai E., Burley S.K.;
RT "Co-crystal structure of the HNF-3/fork head DNA-recognition motif
RT resembles histone H5.";
RL Nature 364:412-420(1993).
CC -!- FUNCTION: Transcription factor that is thought to act as a 'pioneer'
CC factor opening the compacted chromatin for other proteins through
CC interactions with nucleosomal core histones and thereby replacing
CC linker histones at target enhancer and/or promoter sites (By
CC similarity). Originally described as a transcription activator for a
CC number of liver genes such as AFP, albumin, tyrosine aminotransferase,
CC PEPCK, etc. Interacts with the cis-acting regulatory regions of these
CC genes. Involved in glucose homeostasis; binds to and activates
CC transcription from the G6PC1 promoter. Binds to the CYP3A4 promoter and
CC activates its transcription in cooperation with CEBPA. Binds to the
CC CYP3A7 promoter together with members of the CTF/NF-I family. Involved
CC in regulation of neuronal-specific transcription. May be involved in
CC regulation of spermatogenesis. {ECO:0000250,
CC ECO:0000269|PubMed:12695546}.
CC -!- SUBUNIT: Interacts with FOXA2. {ECO:0000269|PubMed:19919681,
CC ECO:0000269|PubMed:8332212}.
CC -!- INTERACTION:
CC P55318; P28329-3: CHAT; NbExp=3; IntAct=EBI-3910364, EBI-25837549;
CC P55318; P22607: FGFR3; NbExp=3; IntAct=EBI-3910364, EBI-348399;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089,
CC ECO:0000269|PubMed:19706729}.
CC -!- TISSUE SPECIFICITY: Expressed in erythroleukemia and hepatoma cell
CC lines and in liver and pancreas. Not expressed in any other cell lines
CC or tissues examined. {ECO:0000269|PubMed:8499623}.
CC -!- DEVELOPMENTAL STAGE: Detected in prenatal liver nuclear extracts (12.4-
CC 27 weeks estimated gestational age). Not detected in postnatal liver
CC samples. {ECO:0000269|PubMed:19706729}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Hepatocyte nuclear factors entry;
CC URL="https://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/foxa3/";
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DR EMBL; L12141; AAA58477.1; -; mRNA.
DR EMBL; AF176114; AAD51980.1; -; Genomic_DNA.
DR EMBL; AF176113; AAD51980.1; JOINED; Genomic_DNA.
DR EMBL; BT006720; AAP35366.1; -; mRNA.
DR EMBL; AK223473; BAD97193.1; -; mRNA.
DR EMBL; EU275778; ABX44664.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57394.1; -; Genomic_DNA.
DR EMBL; BC016024; AAH16024.1; -; mRNA.
DR CCDS; CCDS12677.1; -.
DR PIR; C48924; C48924.
DR RefSeq; NP_004488.2; NM_004497.2.
DR PDB; 1VTN; X-ray; 2.50 A; C=115-215.
DR PDBsum; 1VTN; -.
DR AlphaFoldDB; P55318; -.
DR SMR; P55318; -.
DR BioGRID; 109413; 52.
DR IntAct; P55318; 51.
DR MINT; P55318; -.
DR STRING; 9606.ENSP00000304004; -.
DR iPTMnet; P55318; -.
DR PhosphoSitePlus; P55318; -.
DR BioMuta; FOXA3; -.
DR DMDM; 8247938; -.
DR EPD; P55318; -.
DR jPOST; P55318; -.
DR MassIVE; P55318; -.
DR MaxQB; P55318; -.
DR PaxDb; P55318; -.
DR PeptideAtlas; P55318; -.
DR PRIDE; P55318; -.
DR ProteomicsDB; 56846; -.
DR Antibodypedia; 4191; 100 antibodies from 25 providers.
DR DNASU; 3171; -.
DR Ensembl; ENST00000302177.3; ENSP00000304004.1; ENSG00000170608.3.
DR GeneID; 3171; -.
DR KEGG; hsa:3171; -.
DR MANE-Select; ENST00000302177.3; ENSP00000304004.1; NM_004497.3; NP_004488.2.
DR UCSC; uc002pdr.3; human.
DR CTD; 3171; -.
DR DisGeNET; 3171; -.
DR GeneCards; FOXA3; -.
DR HGNC; HGNC:5023; FOXA3.
DR HPA; ENSG00000170608; Group enriched (intestine, liver, pancreas, stomach).
DR MIM; 602295; gene.
DR neXtProt; NX_P55318; -.
DR OpenTargets; ENSG00000170608; -.
DR PharmGKB; PA201092; -.
DR VEuPathDB; HostDB:ENSG00000170608; -.
DR eggNOG; KOG3563; Eukaryota.
DR GeneTree; ENSGT00940000162453; -.
DR HOGENOM; CLU_027910_0_0_1; -.
DR InParanoid; P55318; -.
DR OMA; NNLMSEP; -.
DR OrthoDB; 1181467at2759; -.
DR PhylomeDB; P55318; -.
DR TreeFam; TF316127; -.
DR PathwayCommons; P55318; -.
DR Reactome; R-HSA-210745; Regulation of gene expression in beta cells.
DR SignaLink; P55318; -.
DR BioGRID-ORCS; 3171; 20 hits in 1103 CRISPR screens.
DR ChiTaRS; FOXA3; human.
DR GeneWiki; FOXA3; -.
DR GenomeRNAi; 3171; -.
DR Pharos; P55318; Tbio.
DR PRO; PR:P55318; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P55318; protein.
DR Bgee; ENSG00000170608; Expressed in ileal mucosa and 75 other tissues.
DR ExpressionAtlas; P55318; baseline and differential.
DR Genevisible; P55318; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0019904; F:protein domain specific binding; IEA:InterPro.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IMP:UniProtKB.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0001678; P:cellular glucose homeostasis; TAS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0007283; P:spermatogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR013638; Fork-head_N.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR018122; TF_fork_head_CS_1.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR Pfam; PF08430; Forkhead_N; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Chromatin regulator; Developmental protein;
KW Differentiation; DNA-binding; Nucleus; Reference proteome; Spermatogenesis;
KW Transcription; Transcription regulation.
FT CHAIN 1..350
FT /note="Hepatocyte nuclear factor 3-gamma"
FT /id="PRO_0000091800"
FT DNA_BIND 116..207
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 217..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..246
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..261
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 91
FT /note="G -> R (in dbSNP:rs758330593)"
FT /id="VAR_008859"
FT CONFLICT 52
FT /note="Missing (in Ref. 1; AAA58477)"
FT /evidence="ECO:0000305"
FT CONFLICT 83
FT /note="V -> L (in Ref. 1; AAA58477)"
FT /evidence="ECO:0000305"
FT CONFLICT 107
FT /note="K -> M (in Ref. 4; BAD97193)"
FT /evidence="ECO:0000305"
FT CONFLICT 111..113
FT /note="RPL -> AP (in Ref. 1; AAA58477)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="M -> V (in Ref. 1; AAA58477)"
FT /evidence="ECO:0000305"
FT CONFLICT 156
FT /note="E -> D (in Ref. 1; AAA58477)"
FT /evidence="ECO:0000305"
FT CONFLICT 227..228
FT /note="AT -> S (in Ref. 1; AAA58477)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="E -> D (in Ref. 1; AAA58477)"
FT /evidence="ECO:0000305"
FT HELIX 122..131
FT /evidence="ECO:0007829|PDB:1VTN"
FT HELIX 140..150
FT /evidence="ECO:0007829|PDB:1VTN"
FT HELIX 152..155
FT /evidence="ECO:0007829|PDB:1VTN"
FT HELIX 158..171
FT /evidence="ECO:0007829|PDB:1VTN"
FT STRAND 175..178
FT /evidence="ECO:0007829|PDB:1VTN"
FT STRAND 190..193
FT /evidence="ECO:0007829|PDB:1VTN"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:1VTN"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:1VTN"
SQ SEQUENCE 350 AA; 37140 MW; 07657D41B0867101 CRC64;
MLGSVKMEAH DLAEWSYYPE AGEVYSPVTP VPTMAPLNSY MTLNPLSSPY PPGGLPASPL
PSGPLAPPAP AAPLGPTFPG LGVSGGSSSS GYGAPGPGLV HGKEMPKGYR RPLAHAKPPY
SYISLITMAI QQAPGKMLTL SEIYQWIMDL FPYYRENQQR WQNSIRHSLS FNDCFVKVAR
SPDKPGKGSY WALHPSSGNM FENGCYLRRQ KRFKLEEKVK KGGSGAATTT RNGTGSAAST
TTPAATVTSP PQPPPPAPEP EAQGGEDVGA LDCGSPASST PYFTGLELPG ELKLDAPYNF
NHPFSINNLM SEQTPAPPKL DVGFGGYGAE GGEPGVYYQG LYSRSLLNAS
